This project is designed to study the pulmonary circulation under both normal and diseased conditions by a multidisciplinary approach. We have devised a versatile intact chest controlled flow technique to study pulmonary vascular responses to physiologic, pharmacologic and pathologic interventions. Intrapulmonary segments of artery and vein are then removed from these animals for correlative studies of vascular smooth muscle cyclic nucleotides, force generation in tissue bath, calcium flux, adrenergic innervation by fluorescent microscopy, and vascular smooth muscle, adrenergic terminals and specialized cells by electron microscopy. Studies of normal and abnormal lungs are planned in these areas: Response to hypoxia in responder and non-responder groups and species; Pulmonary pharmacokinetics; Pulmonary vascular reflexes; The shock syndrome; Chronic lung disease or alterations, including granuloma, vasculitis and remiplanted lung.